Tumor-associated peptide–human leukocyte antigen complexes (pHLAs) represent the largest pool of cell surface–expressed cancer-specific epitopes, making them attractive targets for cancer therapies. Soluble bispecific molecules that incorporate an anti-CD3 effector function are being developed to redirect T cells against these targets using 2 different approaches. The first achieves pHLA recognition via affinity-enhanced versions of natural TCRs (e.g., immune-mobilizing monoclonal T cell receptors against cancer [ImmTAC] molecules), whereas the second harnesses an antibody-based format (TCR-mimic antibodies). For both classes of reagent, target specificity is vital, considering the vast universe of potential pHLA molecules that can be presented on healthy cells. Here, we made use of structural, biochemical, and computational approaches to investigate the molecular rules underpinning the reactivity patterns of pHLA-targeting bispecifics. We demonstrate that affinity-enhanced TCRs engage pHLA using a comparatively broad and balanced energetic footprint, with interactions distributed over several HLA and peptide side chains. As ImmTAC molecules, these TCRs also retained a greater degree of pHLA selectivity, with less off-target activity in cellular assays. Conversely, TCR-mimic antibodies tended to exhibit binding modes focused more toward hot spots on the HLA surface and exhibited a greater degree of crossreactivity. Our findings extend our understanding of the basic principles that underpin pHLA selectivity and exemplify a number of molecular approaches that can be used to probe the specificity of pHLA-targeting molecules, aiding the development of future reagents.

musicisart magazine 2017 Best Music: Slenderbodies

Los Angeles-based duo Slenderbodies create music that feels like your watching the ocean. Slenderbodies recently released their brand new project fabulist out now via Majestic Casual Records. The five-track collection is full of whispers of sensuality found within falsetto vocals accompanied with vibrations of soft guitars melted into funky and soulful bass-lines that collide together […]

The post 2017 Best Music: Slenderbodies appeared first on musicisart magazine.

Recently Donald Trump tweeted the word "TREASON?" in light of the New York Times op ed that was published on Wednesday. The article was supposedly written by someone within the Trump Administration, calling themselves part of the "resistance." 

After Trump's "treason" tweet, people on Twitter began making their own amusing parodies, which you can read below!

Disturbing videos posted online paint a grim picture on how hospitals seem to be struggling to deal with bodies as they battle against the wave of coronavirus patients.

Blood centers are ramping up efforts to collect plasma from people who recovered from COVID-19 in hopes their coronavirus antibodies could save lives.

On the latest episode of "Prime Time," CNN's Chris Cuomo reveals he has recovered from COVID-19 and possesses antibodies. But what does that mean?

Get a taste for the good life at three of UK's top foodie hot spots

The al-Hota gorge became "a place of horror" under the jihadist group, Human Rights Watch says.

• Warm Bodies review
• The History of Zombie Movies That Rudy Likes
• What We Watched: Bob's Burgers, Some Bob Marley documentary, Movie 43 and The Innkeepers

McCune-Albright syndrome (MAS) is a mosaic disorder arising from gain-of-function mutations in the GNAS gene, which encodes the 3', 5'-cyclic adenosine monophosphate (cAMP) pathway-associated G-protein, Gsα. Clinical manifestations of MAS in a given individual, including fibrous dysplasia, are determined by the timing and location of the GNAS mutation during embryogenesis, the tissues involved, and the role of Gsα in the affected tissues. The Gsα mutation results in dysregulation of the cAMP signaling cascade, leading to upregulation of phosphodiesterase type 4 (PDE4), which catalyzes the hydrolysis of cAMP. Increased cAMP levels have been found in vitro in both animal models of fibrous dysplasia and in cultured cells from individuals with MAS, but not in humans with fibrous dysplasia. Positron emission tomography (PET) imaging of PDE4 with ¹¹C-(R)-rolipram has been used successfully to study the in vivo activity of the cAMP cascade. To date, it remains unknown whether fibrous dysplasia and other symptoms of MAS, including neuropsychiatric impairments, are associated with increased PDE4 activity in humans. Methods: ¹¹C-(R)-rolipram whole-body and brain PET scans were performed in six individuals with MAS (three for brain scans and six for whole-body scans) and nine healthy controls (seven for brain scans and six for whole-body scans). Results: ¹¹C-(R)-rolipram binding correlated with known locations of fibrous dysplasia in the periphery of individuals with MAS; no uptake was observed in the bones of healthy controls. In peripheral organs and the brain, no difference in ¹¹C-(R)-rolipram uptake was noted between participants with MAS and healthy controls. Conclusion: This study is the first to find evidence for increased cAMP activity in areas of fibrous dysplasia in vivo. No differences in brain uptake between MAS participants and controls were detected, which could be due to several reasons, including the limited anatomic resolution of PET. Nevertheless, the results confirm the usefulness of PET scans with ¹¹C-(R)-rolipram to indirectly measure increased cAMP pathway activation in human disease.

Proteins that bind carbohydrate structures can serve as tools to quantify or localize specific glycans in biological specimens. Such proteins, including lectins and glycan-binding antibodies, are particularly valuable if accurate information is available about the glycans that a protein binds. Glycan arrays have been transformational for uncovering rich information about the nuances and complexities of glycan-binding specificity. A challenge, however, has been the analysis of the data. Because protein-glycan interactions are so complex, simplistic modes of analyzing the data and describing glycan-binding specificities have proven inadequate in many cases. This review surveys the methods for handling high-content data on protein-glycan interactions. We contrast the approaches that have been demonstrated and provide an overview of the resources that are available. We also give an outlook on the promising experimental technologies for generating new insights into protein-glycan interactions, as well as a perspective on the limitations that currently face the field.

Ankylosing Spondylitis (AS) is a common, inflammatory rheumatic disease, which primarily affects the axial skeleton and is associated with sacroiliitis, uveitis and enthesitis. Unlike other autoimmune rheumatic diseases, such as rheumatoid arthritis or systemic lupus erythematosus, autoantibodies have not yet been reported to be a feature of AS. We therefore wished to determine if plasma from patients with AS contained autoantibodies and if so, characterize and quantify this response in comparison to patients with Rheumatoid Arthritis (RA) and healthy controls. Two high-density nucleic acid programmable protein arrays expressing a total of 3498 proteins were screened with plasma from 25 patients with AS, 17 with RA and 25 healthy controls. Autoantigens identified were subjected to Ingenuity Pathway Analysis in order to determine patterns of signalling cascades or tissue origin. 44% of patients with Ankylosing Spondylitis demonstrated a broad autoantibody response, as compared to 33% of patients with RA and only 8% of healthy controls. Individuals with AS demonstrated autoantibody responses to shared autoantigens, and 60% of autoantigens identified in the AS cohort were restricted to that group. The AS patients autoantibody responses were targeted towards connective, skeletal and muscular tissue, unlike those of RA patients or healthy controls. Thus, patients with AS show evidence of systemic humoral autoimmunity and multispecific autoantibody production. Nucleic Acid Programmable Protein Arrays constitute a powerful tool to study autoimmune diseases.

Catherine Pihoker
Dec 1, 2005; 54:S52-S61
Section II: Type 1-Related Forms of Diabetes

Sisters -- Fiction.

A prominent theory claims that the right temporoparietal junction (rTPJ) is especially associated with embodied processes relevant to perspective-taking. In the present study, we use high-definition transcranial direct current stimulation to provide evidence that the rTPJ is causally associated with the embodied processes underpinning perspective-taking. Eighty-eight young human adults were stratified to receive either rTPJ or dorsomedial PFC anodal high-definition transcranial direct current stimulation in a sham-controlled, double-blind, repeated-measures design. Perspective-tracking (line-of-sight) and perspective-taking (embodied rotation) were assessed using a visuo-spatial perspective-taking task that required understanding what another person could see or how they see it, respectively. Embodied processing was manipulated by positioning the participant in a manner congruent or incongruent with the orientation of an avatar on the screen. As perspective-taking, but not perspective-tracking, is influenced by bodily position, this allows the investigation of the specific causal role for the rTPJ in embodied processing. Crucially, anodal stimulation to the rTPJ increased the effect of bodily position during perspective-taking, whereas no such effects were identified during perspective-tracking, thereby providing evidence for a causal role for the rTPJ in the embodied component of perspective-taking. Stimulation to the dorsomedial PFC had no effect on perspective-tracking or taking. Therefore, the present study provides support for theories postulating that the rTPJ is causally involved in embodied cognitive processing relevant to social functioning.

SIGNIFICANCE STATEMENT The ability to understand another's perspective is a fundamental component of social functioning. Adopting another perspective is thought to involve both embodied and nonembodied processes. The present study used high-definition transcranial direct current stimulation (HD-tDCS) and provided causal evidence that the right temporoparietal junction is involved specifically in the embodied component of perspective-taking. Specifically, HD-tDCS to the right temporoparietal junction, but not another hub of the social brain (dorsomedial PFC), increased the effect of body position during perspective-taking, but not tracking. This is the first causal evidence that HD-tDCS can modulate social embodied processing in a site-specific and task-specific manner.

June 18 was the world’s first Sustainable Gastronomy Day. This begs the questions: 1) What in the world is sustainable gastronomy? 2) Why is it important enough to have a “day” dedicated to it? and 3) Even so, why should I care? What is Sustainable Gastronomy?  Gastronomy is sometimes called the art of food. It can also refer to a style of [...]

Expelled by animals as a waste product, the gas appears to play a crucial role in keeping these bizarre, burrowing rodents safe

Colloidal gold–antibody conjugates are easy to prepare and are an excellent choice for microscopic applications. Colloidal gold is an aqueous suspension of nanometer-sized particles of gold. Typically, chloroauric acid, HAuCl₄, is reduced with dilute solutions of sodium citrate, as described here. This will cause the gold to form small aggregates that will associate with proteins. Gold particles of specific sizes can be isolated and differentiated microscopically, allowing these particles to be used for multiple-label experiments. Colloidal gold-labeled antibodies are widely used in electron microscopy (EM), and can be used for light microscopy but require additional steps (silver enhancement).

There are many uses for antibodies labeled with metal ions. Most of these methods involve first attaching a metal chelator to the antibody molecule. This is achieved using standard cross-linking chemistry and then adding the desired metal at appropriate concentration and pH. The method described here outlines a basic procedure for creating a lanthanide conjugate. Lanthanide conjugates are used for proximity assays, as MRI contrast agents, or for mass cytometry experiments. Different metals and chelators can be substituted, but the basic procedures are similar.

1. Bharat Biotech to lead human monoclonal antibodies project  The Hindu
2. Bharat Biotech leads CSIR project to develop antibodies against Covid-19  Times of India
3. Bharat Biotech To Lead CSIR’s Project To Develop Human Monoclonal Antibodies For Covid-19 Therapy  Swarajya
4. Bharat Biotech to develop human antibodies for COVID-19 therapy  Telangana Today
5. Bharat Biotech vows human monoclonal antibodies to neutralise COVID-19 in 6 months  Mumbai Mirror
6. View Full coverage on Google News

A Ukrainian pastor responds to nearly 100 per cent unemployment in his village by starting biofuel and cash crop business enterprises.

Quiet, crisp and clear winter days are perfect for exploring Scotland’s most spectacular coast and countryside scenery – especially with the promise of a wholesome, heart-warming meal and a cosy room after a day exploring. While Munro-bagging at this time of year might be a little too ambitious, Scotland has no shortage of shorter and more gentle winter walks, all within a stone’s throw of some of Scotland’s best foodie destinations. Here is a selection of Scotland’s top 10 winter walk

Perforation in the setting of retained esophageal foreign body is rare, but can be catastrophic. The role of imaging in screening for injury after removal has not previously been studied.

The rate of esophageal injury among children with retained esophageal foreign body is 1.3%. Intraoperative findings suggestive of injury are predictive of perforation. Routine chest radiography is not warranted in those who do not meet this criterion. (Read the full article)

Sonam, who is currently in Delhi with her husband and in-laws, has been posting pictures of the arrangements of the intimate celebration at the Ahuja household.

They had started their journey on foot from Maharashtra hoping to reach Madhya Pradesh, but it was their bodies that reached their home districts of Shahdol and Umaria by special trains on Saturday...

WILMINGTON, Del. –  Governor John Carney on Friday authorized all meetings of public bodies to be conducted electronically until further notice. Governor Carney on Thursday issued a State of Emergency declaration to prepare for the spread of Coronavirus (COVID-19). The emergency declaration allows the State of Delaware executive branch agencies to conduct public meetings electronically to […]

A coalition of UK associations at the university level, and a few support organizations, has urged the UK government, for improving the student visa system, in meeting its future goals. The goal is to get 600,000 global higher education students in the…

Terming this as one of the first known antibodies to neutralize SARS-CoV-2, Jason McLellan, associate professor of molecular biosciences at UT Austin and co-senior author, made a reference to the virus that causes COVID-19.

Therefore, an alternate therapeutic regimen for early deployment is critical, the vaccine-maker said in the statement.